1. Field of the Invention
The present invention relates to a process for the production of a 3,4-epoxybutyrate and an intermediate therefor. More particularly, the present invention relates to a process for the production of a 3,4-epoxybutyrate from 3,4dihydroxybutyronitile and a 3,4-dihydroxybutyric acid derivative which is useful as an intermediate in the production of the 3,4-epoxybutyrate.
2. Description of the Related Art
A 3,4-epoxybutyrate of the formula: ##STR5## wherein R.sup.1 is an alkyl or aralkyl group is easily converted to carnitine (see U.S. Pat. Nos. 3,830,931 and 3,968,241), which is known as an aperitive and an agent for treating congestive heart failure or arrhythmia (see J. Org. Chem., 53, 104 (1988)).
The 3,4-epoxybutyrate (I) is also known as an important intermediate which can be easily converted to 4-hydroxy-2-oxo-1-pyrrolidineacetamide derivatives including 4-hydroxy-2-oxo-1-pyrrolidineacetamide (oxiracetam) known as an agent for improving cerabral metabolism (see Japanese Patent Kokai Publication Nos. 208957/1985, 461/1987 and 185069/1987).
In addition, the 3,4-epoxybutyrate (I) can be used in the synthesis of .gamma.-amino-.beta.-hydroxybutyric acid (GABOB) which has an antiepileptic activity and an antihypertensive activity.
As above, the 3,4-epoxybutyrate (I) is known to be converted to various biologically active substances or medicines.
To prepare the 3,4-epoxybutyrate, the following major processes are known:
(1) A process comprising epoxidizing a vinyl acetate with a peracid (see J. Pharm. Sci., 64, 1262 (1975) and Japanese Patent Kokai Publication No. 10077/1987).
(2) A process comprising methoxycarbonylating epichlorohydrin with carbon monooxide and methanol to obtain a 4-chloro-3-hydroxybutyrate and cyclizing said ester with silver oxide to obtain a 3,4-epoxybutyrate (see J. Org. Chem., 32, 3888 (1967).
However, the first process has problems such as handling of the organic peracid which is inherently corrosive and dangerous in mass scale and the use of heavy metal catalysts such as tungsten.
Since the 3,4-epoxybutyrate (I) has one asymmetric carbon atom in a molecule, it contains two (R)- and (S)-enantiomers and further isomers of the ester (I) include the (RS)-isomer (racemic mixture), (R)-isomer (optically active) and (S)-isomer (optically active).
Recently, utility of optically active substances is increased in various fields such as pharmaceutical, agricultural and liquid crystal fields. By the above process (1), only the (RS)-isomer (racemic mixture) can be produced. Optical resolution of the racemic mixture with an enzyme is known (see Japanese Patent Kokai Publication Nos. 272983/1987 and 272984/1987). However, this optical resolution can provide only the (R)-isomer and the optical purity is unsatisfactory for some alkyl groups of the ester.
By the process (1), no pure (S)-isomer is produced and pure (R)-isomers are produced for some esters. Therefore, it is desired to provide a process for producing both optical active isomers of the 3,4-epoxybutyrate (I).
The above process (2) is not a commercially attractive process because it uses toxic carbon monooxide and produces the product only in a low yield, and silver oxide to be used for cyclization is expensive and should be recovered.